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J. Virol. doi:10.1128/JVI.00775-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Measles virus-induced block of transendothelial migration of T lymphocytes and infection-mediated virus spread across endothelial cell barriers

Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany; Institute of Virology, University of Marburg, 35043 Marburg, Germany; Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

^* To whom correspondence should be addressed. Email: jss{at}vim.uni-wuerzburg.de.

	Abstract

In order to analyze whether measles virus (MV) is transported via transmigrating leukocytes across endothelial barriers, or whether virus spreads via infection of endothelial cells and basolateral release, we investigated the migratory behaviour of infected human primary T lymphocytes across polarized cell layers of human brain microvascular endothelial cells (HBMEC). We found that the capacity of lymphocytes to migrate through filter pores was only slightly affected by wildtype MV infection, whereas their capacity to migrate through endothelial barriers was drastically reduced. MV-infection stimulated the expression and activation of the leukocyte integrins LFA-1 and VLA-4 mediating a strong adherence to the surface of endothelial cells. Furthermore, the formation of engulfing membrane protrusions by endothelial cells, so called transmigratory cups, was induced, but transmigration was impaired. As a consequence of this close cell-cell contact, MV infection was transmitted from lymphocytes to the endothelium. MV envelope proteins were expressed on the apical and basolateral surface of infected polarized endothelial cells, and virus was released from both sides. Wildtype MV-infection did not induce the formation of syncytia suggesting virus spread from cell-to-cell via cell processes and contacts. Our data indicate that transendothelial migration of infected T cells is strongly inhibited, whereas virus can cross endothelial barriers by productive infection of the endothelium and subsequent bipolar virus release.